6-136858311-C-T

Variant names:

• chr6-136858311-C-T
• rs717088
• NM_000288.4:c.527-8316C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000288.4(PEX7):​c.527-8316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,036 control chromosomes in the GnomAD database, including 31,078 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31078 hom., cov: 32)
• Consequence: PEX7 NM_000288.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 5 publications found

Genes affected

PEX7 (HGNC:8860): (peroxisomal biogenesis factor 7) This gene encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Defects in this gene cause peroxisome biogenesis disorders (PBDs), which are characterized by multiple defects in peroxisome function. There are at least 14 complementation groups for PBDs, with more than one phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene have been associated with PBD complementation group 11 (PBD-CG11) disorders, rhizomelic chondrodysplasia punctata type 1 (RCDP1), and Refsum disease (RD). [provided by RefSeq, Oct 2008]

PEX7 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 9B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• rhizomelic chondrodysplasia punctata type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• adult Refsum disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX7	NM_000288.4	c.527-8316C>T		intron_variant	Intron 5 of 9	ENST00000318471.5	NP_000279.1
PEX7	NM_001410945.1	c.413-8316C>T		intron_variant	Intron 5 of 9		NP_001397874.1
PEX7	XM_006715502.3	c.340-11579C>T		intron_variant	Intron 3 of 6		XP_006715565.1
PEX7	XM_047418874.1	c.526+12130C>T		intron_variant	Intron 5 of 5		XP_047274830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000318471.5	c.527-8316C>T		intron_variant	Intron 5 of 9	1	NM_000288.4	ENSP00000315680.3

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96933 AN: 151918 Hom.: 31052 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.631

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.638 AC: 97015 AN: 152036 Hom.: 31078 Cov.: 32 AF XY: 0.635 AC XY: 47169 AN XY: 74300

African (AFR) AF: 0.691 AC: 28631 AN: 41458

American (AMR) AF: 0.633 AC: 9673 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2290 AN: 3472

East Asian (EAS) AF: 0.532 AC: 2749 AN: 5166

South Asian (SAS) AF: 0.620 AC: 2986 AN: 4814

European-Finnish (FIN) AF: 0.586 AC: 6185 AN: 10560

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42564 AN: 67980

Other (OTH) AF: 0.633 AC: 1336 AN: 2112

Alfa AF: 0.628 Hom.: 17631

Bravo AF: 0.640

Asia WGS AF: 0.632 AC: 2196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.53
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs717088; hg19: chr6-137179449;